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Polypurine tract modified retroviral vectors

a technology of polypurine tract and retroviral vector, which is applied in the field of integration-defective retroviral vector, can solve the problem of limiting the use of in vivo gene transfer to non-proliferating cells

Active Publication Date: 2018-07-10
THE UNIV OF NORTH CAROLINA AT CHAPEL HILL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This can limit their use for in vivo gene transfer to non-proliferating cells such as hepatocytes, myofibers, hematopoietic stein cells (HSCs), and neurons.
A key challenge for gene transfer based on the use of retroviral vectors is to achieve stable transgene expression while minimizing insertional mutagenesis and induction of the DNA damage response due to the presence of double stranded DNA.

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  • Polypurine tract modified retroviral vectors
  • Polypurine tract modified retroviral vectors
  • Polypurine tract modified retroviral vectors

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Embodiment Construction

[0034]The ability of retroviral vectors to deliver large genetic payloads into non-dividing cells opens promising avenues for the introduction of one or more particular nucleic acid sequences into a cell. However, realizing the full potential of the retroviral vector system into a valid delivery modality is currently impeded by the potential for retroviral vector-induced insertional mutagenesis. Accordingly, the presently disclosed subject matter provides integration-deficient retroviral vectors, and methods of making and using the same, that address the risks associated with retroviral vector-mediated insertional mutagenesis, among other problems in the art.

[0035]Previous approaches for producing non-integrating retroviral vectors are premised on inhibiting the integration step of the vector life cycle during which the linear vector DNA is inserted into the host genome. In these previously described approaches, non-integrating retroviral vectors are generated by either employing in...

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Abstract

An integration-defective retroviral vector transfer cassette lacking a functional polypurine tract (PPT) is provided. Also provided are isolated nucleic acids that include a heterologous nucleotide sequence, one or two retroviral long terminal repeats (LTRs), a packaging signal, a rev responsive element, and a eukaryotic promoter, wherein the nucleic acid lacks a functional PPT; vectors that include the disclosed isolated nucleic acids; recombinant retroviral particles and mRNAs thereof; retroviral vector kits; and methods for producing integration-defective vector particles, achieving gene expression of a nucleotide sequence of interest, and inserting a nucleotide sequence of interest into a host cell genome in a site-specific or non-specific manner.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation application of, and claims priority to, U.S. patent application Ser. No. 12 / 747,076, filed Aug. 27, 2010, and issued as U.S. Pat. No. 9,796,087 on Oct. 24, 2017, which claims the benefit of PCT International Application No. PCT / US08 / 86409, filed Dec. 11, 2008, which claims priority to U.S. Provisional Patent Application Ser. No. 61 / 007,118 filed Dec. 11, 2007, the disclosure of each of which is incorporated herein by reference in its entirety.STATEMENT OF GOVERNMENT INTEREST[0002]This invention was made with government support under Grant No. 2R56DK058702-06A1 awarded by the National Institutes of Health. The government has certain rights in the invention.TECHNICAL FIELD[0003]The presently disclosed subject matter pertains to integration-defective retroviral vectors and methods for using the same, such as in gene therapy and in basic biology research.BACKGROUND[0004]The capacity to introduce a particular...

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): C12P19/34C12N15/86C12N15/63C12N15/67C12N7/01C12N5/10
CPCC12N15/86C12N2740/15043C12N2800/24C12N2800/108C12N2740/16043
Inventor KAFRI, TAL
Owner THE UNIV OF NORTH CAROLINA AT CHAPEL HILL